IL-27 signalling promotes adipocyte thermogenesis and energy expenditure.

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

Zn-based batteries for sustainable energy storage: strategies and mechanisms.

Batteries play a pivotal role in various electrochemical energy storage systems, functioning as essential components to enhance energy utilization efficiency and expedite the realization of energy and environmental sustainability. Zn-based batteries have attracted increasing attention as a promising alternative to lithium-ion batteries owing to their cost effectiveness, enhanced intrinsic safety, and favorable electrochemical performance. In this context, substantial endeavors have been dedicated to crafting and advancing high-performance Zn-based batteries. However, some challenges, including limited discharging capacity, low operating voltage, low energy density, short cycle life, and complicated energy storage mechanism, need to be addressed in order to render large-scale practical applications. In this review, we comprehensively present recent advances in designing high-performance Zn-based batteries and in elucidating energy storage mechanisms. First, various redox mechanisms in Zn-based batteries are systematically summarized, including insertion-type, conversion-type, coordination-type, and catalysis-type mechanisms. Subsequently, the design strategies aiming at enhancing the electrochemical performance of Zn-based batteries are underscored, focusing on several aspects, including output voltage, capacity, energy density, and cycle life. Finally, challenges and future prospects of Zn-based batteries are discussed.

Salicylic acid regulates two photosystem II protection pathways in tomato under chilling stress mediated by ETHYLENE INSENSITIVE 3-like proteins.

Chilling stress seriously impairs photosynthesis and activates a series of molecular responses in plants. Previous studies have shown that ETHYLENE INSENSITIVE 3 (EIN3) and EIN3-like (SlEIL) proteins mediate ethylene signaling and reduce plant tolerance to freezing in tomato (Solanum lycopersicum). However, the specific molecular mechanisms underlying an EIN3/EILs-mediated photoprotection pathway under chilling stress are unclear. Here, we discovered that salicylic acid (SA) participates in photosystem II (PSII) protection via SlEIL2 and SlEIL7. Under chilling stress, the phenylalanine ammonia-lyase gene SlPAL5 plays an important role in the production of SA, which also induces WHIRLY1 (SlWHY1) transcription. The resulting accumulation of SlWHY1 activates SlEIL7 expression under chilling stress. SlEIL7 then binds to and blocks the repression domain of the heat shock factor SlHSFB-2B, releasing its inhibition of HEAT SHOCK PROTEIN 21 (HSP21) expression to maintain PSII stability. In addition, SlWHY1 indirectly represses SlEIL2 expression, allowing the expression of l-GALACTOSE-1-PHOSPHATE PHOSPHATASE3 (SlGPP3). The ensuing higher SlGPP3 abundance promotes the accumulation of ascorbic acid (AsA), which scavenges reactive oxygen species produced upon chilling stress and thus protects PSII. Our study demonstrates that SlEIL2 and SlEIL7 protect PSII under chilling stress via two different SA response mechanisms: one involving the antioxidant AsA and the other involving the photoprotective chaperone protein HSP21.

Natural variations in the PbCPK28 promoter regulate sugar content through interaction with PbTST4 and PbVHA-A1 in pear.

Soluble sugars play an important role in plant growth, development and fruit quality. Pear fruits have demonstrated a considerable improvement in sugar quality during their long history of selection. However, little is known about the underlying molecular mechanisms accompanying the changes in fruit sugar content as a result of selection by horticulturists. Here, we identified a calcium-dependent protein kinase (PbCPK28), which is located on LG15 and is present within a selective sweep region, thus linked to the quantitative trait loci for soluble solids. Association analysis indicates that a single nucleotide polymorphism-13 variation (SNP13T/C ) in the PbCPK28 regulatory region led to fructose content diversity in pear. Elevated expression of PbCPK28 resulted in significantly increased fructose levels in pear fruits. Furthermore, PbCPK28 interacts with and phosphorylates PbTST4, a proton antiporter, thereby coupling the sugar import into the vacuole with proton export. We demonstrated that residues S277 and S314 of PbTST4 are crucial for its function. Additionally, PbCPK28 interacts with and phosphorylates the vacuolar hydrogen proton pump PbVHA-A1, which could provide proton motive forces for PbTST4. We also found that the T11 and Y120 phosphorylation sites in PbVHA-A1 are essential for its function. Evolution analysis and yeast-two-hybrid results support that the CPK-TST/CPK-VHA-A regulatory network is highly conserved in plants, especially the corresponding phosphorylation sites. Together, our work identifies an agriculturally important natural variation and an important regulatory network, allowing genetic improvement of fruit sugar contents in pears through modulation of PbCPK28 expression and phosphorylation of PbTST4 and PbVHA-A1.

Self S-RNase inhibits ABF-LRX signaling to arrest pollen tube growth to achieve self-incompatibility in pear.

Gametophytic self-incompatibility (GSI) has been widely studied in flowering plants, but studies of the mechanisms underlying pollen tube growth arrest by self S-RNase in GSI species are limited. In the present study, two leucine-rich repeat extensin genes in pear (Pyrus bretschneideri), PbLRXA2.1 and PbLRXA2.2, were identified based on transcriptome and quantitative real-time PCR analyses. The expression levels of these two LRX genes were significantly higher in the pollen grains and pollen tubes of the self-compatible cultivar 'Jinzhui' (harboring a spontaneous bud mutation) than in those of the self-incompatible cultivar 'Yali'. Both PbLRXA2.1 and PbLRXA2.2 stimulated pollen tube growth and attenuated the inhibitory effects of self S-RNase on pollen tube growth by stabilizing the actin cytoskeleton and enhancing cell wall integrity. These results indicate that abnormal expression of PbLRXA2.1 and PbLRXA2.2 is involved in the loss of self-incompatibility in 'Jinzhui'. The PbLRXA2.1 and PbLRXA2.2 promoters were directly bound by the ABRE-binding factor PbABF.D.2. Knockdown of PbABF.D.2 decreased PbLRXA2.1 and PbLRXA2.2 expression and inhibited pollen tube growth. Notably, the expression of PbLRXA2.1, PbLRXA2.2, and PbABF.D.2 was repressed by self S-RNase, suggesting that self S-RNase can arrest pollen tube growth by restricting the PbABF.D.2-PbLRXA2.1/PbLRXA2.2 signal cascade. These results provide novel insight into pollen tube growth arrest by self S-RNase.

Gene expression and expression quantitative trait loci analyses uncover natural variations underlying the improvement of important agronomic traits during modern maize breeding.

Maize (Zea mays L.) is a major staple crop worldwide, and during modern maize breeding, cultivars with increased tolerance to high-density planting and higher yield per plant have contributed significantly to the increased yield per unit land area. Systematically identifying key agronomic traits and their associated genomic changes during modern maize breeding remains a significant challenge because of the complexity of genetic regulation and the interactions of the various agronomic traits, with most of them being controlled by numerous small-effect quantitative trait loci (QTLs). Here, we performed phenotypic and gene expression analyses for a set of 137 elite inbred lines of maize from different breeding eras in China. We found four yield-related traits are significantly improved during modern maize breeding. Through gene-clustering analyses, we identified four groups of expressed genes with distinct trends of expression pattern change across the historical breeding eras. In combination with weighted gene co-expression network analysis, we identified several candidate genes regulating various plant architecture- and yield-related agronomic traits, such as ZmARF16, ZmARF34, ZmTCP40, ZmPIN7, ZmPYL10, ZmJMJ10, ZmARF1, ZmSWEET15b, ZmGLN6 and Zm00001d019150. Further, by combining expression quantitative trait loci (eQTLs) analyses, correlation coefficient analyses and population genetics, we identified a set of candidate genes that might have been under selection and contributed to the genetic improvement of various agronomic traits during modern maize breeding, including a number of known key regulators of plant architecture, flowering time and yield-related traits, such as ZmPIF3.3, ZAG1, ZFL2 and ZmBES1. Lastly, we validated the functional variations in GL15, ZmPHYB2 and ZmPYL10 that influence kernel row number, flowering time, plant height and ear height, respectively. Our results demonstrates the effectiveness of our combined approaches for uncovering key candidate regulatory genes and functional variation underlying the improvement of important agronomic traits during modern maize breeding, and provide a valuable genetic resource for the molecular breeding of maize cultivars with tolerance for high-density planting.

Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.

BACKGROUND: Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties. RESULTS: By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level. CONCLUSION: This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.

Strategies Toward High Selectivity, Activity, and Stability of Single-Atom Catalysts.

Single-atom catalysts (SACs) hold immense promise in facilitating the rational use of metal resources and achieving atomic economy due to their exceptional atom-utilization efficiency and distinct characteristics. Despite the growing interest in SACs, only limited reviews have holistically summarized their advancements centering on performance metrics. In this review, first, a thorough overview on the research progress in SACs is presented from a performance perspective and the strategies, advancements, and intriguing approaches employed to enhance the critical attributes in SACs are discussed. Subsequently, a comprehensive summary and critical analysis of the electrochemical applications of SACs are provided, with a particular focus on their efficacy in the oxygen reduction reaction , oxygen evolution reaction, hydrogen evolution reaction , CO2 reduction reaction, and N2 reduction reaction . Finally, the outline future research directions on SACs by concentrating on performance-driven investigation, where potential areas for improvement are identified and promising avenues for further study are highlighted, addressing challenges to unlock the full potential of SACs as high-performance catalysts.

Anchoring Carbon Spheres on Titanium Dioxide Modified Commercial Polyethylene (PE) Separator to Suppress Lithium Dendrites for Lithium Metal Batteries.

Lithium dendrites are easily generated for excessively-solved lithium ions (Li+) inside the lithium metal batteries, which will lead serious safety issues. In this experiment, carbon spheres (CS) are successfully anchored on TiO2 (CS@TiO2) in the hydrothermal polymerization, which is filtrated on the commercial PE separator (CS@TiO2@PE). The negative charge in CS can suppress random diffusion of anions through electrostatic interactions. Density functional theory (DFT) calculations show that CS contributes to the desolvation of Li+, thereby increasing the migration rate of Li+. Furthermore, TiO2 exhibits high affinity to liquid electrolytes and acts as a physical barrier to lithium dendrite formation. CS@TiO2 is a combination of the advantages of CS and TiO2. As results, the Li+ transference number of the CS@TiO2@PE separator can be promoted to 0.63. The Li||Li cell with the CS@TiO2@PE separator exhibits a stable cycle performance for more than 600 h and lower polarization voltage (17 mV) at 1 mA cm-2. The coulombic efficiency (CE) of the Li||Cu cells employe the CS@TiO2@PE separator is 81.63% over 130 cycles. The discharge capacity of LiFePO4||Li cells based on the CS@TiO2@PE separator is 1.73 mAh (capacity retention = 91.53% after 260 cycles). Thus, the CS@TiO2 layer inhibits lithium dendrite formation.

Development and anatomy of petals with specialized nectar holder and pollen container in Fumarioideae (Papaveraceae).

MAIN CONCLUSION: Petal developmental characteristics in Fumarioideae were similar at early stages, and the specialized nectar holder/pollen container formed by the outer/inner petals. The micro-morphology of these two structures, however, shows diversity in seven species. Elaborate petals have been modified to form different types, including petal lobes, ridges, protuberances, and spurs, each with specialized functions. Nectar holder and pollen container presumably have a function in plant-pollinator interactions. In Fumarioideae, four elaborate petals of the disymmetric/zygomorphic flower present architecture forming the "nectar holder" and "pollen container" structure at the bottom and top separately. In the present study, the petals of seven species in Fumarioideae were investigated by scanning electron microscopy, light microscope, and transmission electron microscopes. The results show that petal development could divided into six stages: initiation, enlargement, adaxial/abaxial differentiation, elaborate specializations (sacs, spurs, and lobes formed), extension, and maturation, while the specialized "nectar holder" and "pollen container" structures mainly formed in stage 4. "Nectar holder" is developed from the shallow sac/spur differentiated at the base of the outer petal, eventually forming a multi-organized complex structure, together with staminal nectaries (1-2) with individual sizes. A semi-closed ellipsoidal "pollen container" is developed from the apical part of the 3-lobed inner petals fused by middle lobes and attain different sizes. The adaxial epidermis cells are specialized, with more distinct punctate/dense columnar protrusions or wavy cuticles presented on obviously thickening cell walls. In addition, a large and well-developed cavity appears between the inner and outer epidermis of the petals. As an exception, Hypecoum erectum middle lobes present stamen mimicry. Elaborate petal structure is crucial for comprehending the petal diversity in Fumarioideae and provides more evidence for further exploration of the reproductive study in Papaveraceae.

Comprehensive genomic analysis of Brevibacillus brevis BF19 reveals its biocontrol potential against bitter gourd wilt.

Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

ETHYLENE-INSENSITIVE 3-LIKE 2 regulates ß-carotene and ascorbic acid accumulation in tomatoes during ripening.

ETHYLENE-INSENSITIVE 3/ETHYLENE-INSENSITIVE 3-LIKEs (EIN3/EILs) are important ethylene response factors during fruit ripening. Here, we discovered that EIL2 controls carotenoid metabolism and ascorbic acid (AsA) biosynthesis in tomato (Solanum lycopersicum). In contrast to the red fruits presented in the wild type (WT) 45 d after pollination, the fruits of CRISPR/Cas9 eil2 mutants and SlEIL2 RNA interference lines (ERIs) showed yellow or orange fruits. Correlation analysis of transcriptome and metabolome data for the ERI and WT ripe fruits revealed that SlEIL2 is involved in ß-carotene and AsA accumulation. ETHYLENE RESPONSE FACTORs (ERFs) are the typical components downstream of EIN3 in the ethylene response pathway. Through a comprehensive screening of ERF family members, we determined that SlEIL2 directly regulates the expression of 4 SlERFs. Two of these, SlERF.H30 and SlERF.G6, encode proteins that participate in the regulation of LYCOPENE-ß-CYCLASE 2 (SlLCYB2), encoding an enzyme that mediates the conversion of lycopene to carotene in fruits. In addition, SlEIL2 transcriptionally repressed L-GALACTOSE 1-PHOSPHATE PHOSPHATASE 3 (SlGPP3) and MYO-INOSITOL OXYGENASE 1 (SlMIOX1) expression, which resulted in a 1.62-fold increase of AsA via both the L-galactose and myoinositol pathways. Overall, we demonstrated that SlEIL2 functions in controlling ß-carotene and AsA levels, providing a potential strategy for genetic engineering to improve the nutritional value and quality of tomato fruit.

Time-dependent efficacy analysis of first-line immunotherapies for advanced non-small cell lung cancer.

BACKGROUND: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. METHODS: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. RESULTS: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. CONCLUSIONS: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.

Brominated Flame Retardants (BFRs) in China Over the Past Half-Century: Stocks, Flows, Fates, and Ecological Risks.

China is a significant producer and consumer of various brominated flame retardants (BFRs), raising environmental concerns due to their widespread presence and potential threats to ecosystems and organisms. This study adopts a life cycle perspective, combining material flow analysis, multimedia environmental modeling, and ecological risk assessment to systematically analyze the substance metabolism and ecological risks of six BFR types in China from 1970 to 2021. The findings reveal that China's cumulative BFR consumption reached 3.3 Mt, with the electronics sector being the predominant contributor at 52.1%. Consequently, 1.5 kt of BFRs were released into the environment, with 24.9%, 31.5%, and 43.6% being discharged into the air, water, and soil, respectively. Notably, the proportion of novel BFRs in emissions has steadily increased over the years, exemplified by the increase in decabromodiphenyl ethane (DBDPE) from 21.3% in 2010 to 30.1% in 2021. Geographically, BFR concentrations are higher in the eastern and southwestern regions compared to those in the northwest. Presently, certain BFRs like tetrabromobisphenol A (TBBPA) and DBDPE exhibit moderate to high ecological risks, primarily concentrated in the Shandong and Sichuan provinces. A combination of efficient recycling, emission control, and substitution with novel flame-retardant can minimize the exposure of BFRs to the environment and organisms.

γ-Aminobutyric Acid-Ergic Development Contributes to the Enhancement of Electroencephalogram Slow-Delta Oscillations Under Volatile Anesthesia in Neonatal Rats.

BACKGROUND: General anesthetics (eg, propofol and volatile anesthetics) enhance the slow-delta oscillations of the cortical electroencephalogram (EEG), which partly results from the enhancement of (γ-aminobutyric acid [GABA]) γ-aminobutyric acid-ergic (GABAergic) transmission. There is a GABAergic excitatory-inhibitory shift during postnatal development. Whether general anesthetics can enhance slow-delta oscillations in the immature brain has not yet been unequivocally determined. METHODS: Perforated patch-clamp recording was used to confirm the reversal potential of GABAergic currents throughout GABAergic development in acute brain slices of neonatal rats. The power density of the electrocorticogram and the minimum alveolar concentrations (MAC) of isoflurane and/or sevoflurane were measured in P4-P21 rats. Then, the effects of bumetanide, an inhibitor of the Na + -K + -2Cl - cotransporter (NKCC1) and K + -Cl - cotransporter (KCC2) knockdown on the potency of volatile anesthetics and the power density of the EEG were determined in vivo. RESULTS: Reversal potential of GABAergic currents were gradually hyperpolarized from P4 to P21 in cortical pyramidal neurons. Bumetanide enhanced the hypnotic effects of volatile anesthetics at P5 (for MAC LORR , isoflurane: 0.63% ± 0.07% vs 0.81% ± 0.05%, 95% confidence interval [CI], -0.257 to -0.103, P < .001; sevoflurane: 1.46% ± 0.12% vs 1.66% ± 0.09%, 95% CI, -0.319 to -0.081, P < .001); while knockdown of KCC2 weakened their hypnotic effects at P21 in rats (for MAC LORR , isoflurane: 0.58% ± 0.05% to 0.77% ± 0.20%, 95% CI, 0.013-0.357, P = .003; sevoflurane: 1.17% ± 0.04% to 1.33% ± 0.04%, 95% CI, 0.078-0.244, P < .001). For cortical EEG, slow-delta oscillations were the predominant components of the EEG spectrum in neonatal rats. Isoflurane and/or sevoflurane suppressed the power density of slow-delta oscillations rather than enhancement of it until GABAergic maturity. Enhancement of slow-delta oscillations under volatile anesthetics was simulated by preinjection of bumetanide at P5 (isoflurane: slow-delta changed ratio from -0.31 ± 0.22 to 1.57 ± 1.15, 95% CI, 0.67-3.08, P = .007; sevoflurane: slow-delta changed ratio from -0.46 ± 0.25 to 0.95 ± 0.97, 95% CI, 0.38-2.45, P = .014); and suppressed by KCC2-siRNA at P21 (isoflurane: slow-delta changed ratio from 16.13 ± 5.69 to 3.98 ± 2.35, 95% CI, -18.50 to -5.80, P = .002; sevoflurane: slow-delta changed ratio from 0.13 ± 2.82 to 3.23 ± 2.49, 95% CI, 3.02-10.79, P = .003). CONCLUSIONS: Enhancement of cortical EEG slow-delta oscillations by volatile anesthetics may require mature GABAergic inhibitory transmission during neonatal development.

How consistent are the key recommendations, and what is the quality of guidelines and expert consensus regarding paediatric cow's milk protein allergy?

The objective of this study was to assess the quality and consistency of recommendations in clinical practice guidelines (CPGs) and expert consensus on paediatric cow's milk protein allergy (CMPA) to serve as a foundation for future revisions and enhancements of clinical guidelines and consensus documents. We conducted a comprehensive literature search across several databases, including the Chinese Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, UpToDate, ClinicalKey, DynaMed Plus and BMJ Best Practice. We spanned the search period from the inception of each database through October 1, 2023. We integrated subject headings (MeSH/Emtree) and keywords into the search strategy, used the search methodologies of existing literature and developed it in collaboration with a librarian. Two trained researchers independently conducted the literature screening and data extraction. We evaluated methodological quality and recommendations by using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and AGREE-Recommendations for Excellence (AGREE-REX) tools. Moreover, we compared and summarized key recommendations from high-quality CPGs. Our study included 27 CPGs and expert consensus documents on CMPA. Only four CPGs (14.8%) achieved a high-quality AGREE II rating. The four high-quality CPGs consistently provided recommendations for CMPA. The highest scoring domains for AGREE II were 'scope and purpose' (77 ± 12%) and 'clarity of presentation' (75 ± 22%). The lowest scoring domains were 'stakeholder involvement' (49 ± 21%), 'rigor of development' (34 ± 20%) and 'applicability' (12 ± 20%). Evaluation with AGREE-REX generally demonstrated low scores across its domains.   Conclusion: Recommendations within high-quality CPGs for the paediatric CMPA showed fundamental consistency. Nevertheless, the methodology and recommendation content of CPGs and the expert consensus exhibited low quality, thus indicating a substantial scope for enhancement. Guideline developers should rigorously follow the AGREE II and AGREE-REX standards in creating CPGs or expert consensuses to guarantee their clinical efficacy in managing paediatric CMPA. What is Known: • The quality of clinical practice guidelines and expert consensus on paediatric cow's milk protein allergy (CMPA) remains uncertain. • There is a lack of clarity regarding the consistency of crucial recommendations for CMPA management. What is New: • Improving the methodological quality of guidelines and consensus on CMPA requires greater emphasis on stakeholder engagement, rigorous development processes, and practical applicability. • The recommendations from four high-quality guidelines align. However, addressing clinical applicability, integrating values and preferences, and ensuring actionable implementation are critical to improving the quality of all guidelines.

Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer: A Randomized Controlled Trial.

BACKGROUND The concept of driving pressure (ΔP) has been established to optimize mechanical ventilation-induced lung injury. However, little is known about the specific effects of setting individualized positive end-expiratory pressure (PEEP) with driving pressure guidance on patient diaphragm function. MATERIAL AND METHODS Ninety patients were randomized into 3 groups, with PEEP set to 0 in group C; 5 cmH2O in group F; and individualized PEEP in group I, based on esophageal manometry. Diaphragm ultrasound was performed in the supine position at 6 consecutive time points from T0-T5: diaphragm excursion, end-expiratory diaphragm thickness (Tdi-ee), and diaphragm thickening fraction (DTF) were measured. Primary indicators included diaphragm excursion, Tdi-ee, and DTF at T0-T5, and the correlation between postoperative DTF and ΔP. Secondary indicators included respiratory mechanics, hemodynamic changes at intraoperative d0-d4 time points, and postoperative clinical pulmonary infection scores. RESULTS (1) Diaphragm function parameters reached the lowest point at T1 in all groups (P<0.001). (2) Compared with group C, diaphragm excursion decreased, Tdi-ee increased, and DTF was lower in groups I and F at T1-T5, with significant differences (P<0.05), but the differences between groups I and F were not significant (P>0.05). (3) DTF was significantly and positively correlated with mean intraoperative ΔP in each group at T3, and the correlation was stronger at higher levels of ΔP. CONCLUSIONS Individualized PEEP, achieved by esophageal manometry, minimizes diaphragmatic injury caused by mechanical ventilation based on lung protection, but its protection of the diaphragm during laparoscopic surgery is not superior to that of conventional ventilation strategies.

Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback.

Unlike their natural counterparts, synthetic genetic circuits are usually fragile in the face of environmental perturbations and genetic mutations. Several theoretical robust genetic circuits have been designed, but their performance under real-world conditions has not yet been carefully evaluated. Here, we designed and synthesized a new robust perfect adaptation circuit composed of two-node negative feedback coupling with linear positive feedback on the buffer node. As a key feature, the linear positive feedback was fine-tuned to evaluate its necessity. We found that the desired function was robustly achieved when genetic parameters were varied by systematically perturbing all interacting parts within the topology, and the necessity of the completeness of the topological structures was evaluated by destroying key circuit features. Furthermore, different environmental perturbances were imposed onto the circuit by changing growth rates, carbon metabolic strategies and even chassis cells, and the designed perfect adaptation function was still achieved under all conditions. The successful design of a robust perfect adaptation circuit indicated that the top-down design strategy is capable of predictably guiding bottom-up engineering for robust genetic circuits. This robust adaptation circuit could be integrated as a motif into more complex circuits to robustly implement more sophisticated and critical biological functions.

Robust wrinkled MoS2/N-C bifunctional electrocatalysts interfaced with single Fe atoms for wearable zinc-air batteries.

The ability to create highly efficient and stable bifunctional electrocatalysts, capable of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in the same electrolyte, represents an important endeavor toward high-performance zinc-air batteries (ZABs). Herein, we report a facile strategy for crafting wrinkled MoS2/N-doped carbon core/shell nanospheres interfaced with single Fe atoms (denoted MoS2@Fe-N-C) as superior ORR/OER bifunctional electrocatalysts for robust wearable ZABs with a high capacity and outstanding cycling stability. Specifically, the highly crumpled MoS2 nanosphere core is wrapped with a layer of single-Fe-atom-impregnated, N-doped carbon shell (i.e., Fe-N-C shell with well-dispersed FeN4 sites). Intriguingly, MoS2@Fe-N-C nanospheres manifest an ORR half-wave potential of 0.84 V and an OER overpotential of 360 mV at 10 mA⋅cm-2 More importantly, density functional theory calculations reveal the lowered energy barriers for both ORR and OER, accounting for marked enhanced catalytic performance of MoS2@Fe-N-C nanospheres. Remarkably, wearable ZABs assembled by capitalizing on MoS2@Fe-N-C nanospheres as an air electrode with an ultralow area loading (i.e., 0.25 mg⋅cm-2) display excellent stability against deformation, high special capacity (i.e., 442 mAh⋅g-1Zn), excellent power density (i.e., 78 mW⋅cm-2) and attractive cycling stability (e.g., 50 cycles at current density of 5 mA⋅cm-2). This study provides a platform to rationally design single-atom-interfaced core/shell bifunctional electrocatalysts for efficient metal-air batteries.

Operando unraveling photothermal-promoted dynamic active-sites generation in NiFe2O4 for markedly enhanced oxygen evolution.

The ability to develop highly active and low-cost electrocatalysts represents an important endeavor toward accelerating sluggish water-oxidation kinetics. Herein, we report the implementation and unraveling of the photothermal effect of spinel nanoparticles (NPs) on promoting dynamic active-sites generation to markedly enhance their oxygen evolution reaction (OER) activity via an integrated operando Raman and density functional theory (DFT) study. Specifically, NiFe2O4 (NFO) NPs are first synthesized by capitalizing on amphiphilic star-like diblock copolymers as nanoreactors. Upon the near-infrared light irradiation, the photothermal heating of the NFO-based electrode progressively raises the temperature, accompanied by a marked decrease of overpotential. Accordingly, only an overpotential of 309 mV is required to yield a high current density of 100 mA cm-2, greatly lower than recently reported earth-abundant electrocatalysts. More importantly, the photothermal effect of NFO NPs facilitates surface reconstruction into high-active oxyhydroxides at lower potential (1.36 V) under OER conditions, as revealed by operando Raman spectroelectrochemistry. The DFT calculation corroborates that these reconstructed (Ni,Fe)oxyhydroxides are electrocatalytically active sites as the kinetics barrier is largely reduced over pure NFO without surface reconstruction. Given the diversity of materials (metal oxides, sulfides, phosphides, etc.) possessing the photo-to-thermal conversion, this effect may thus provide a unique and robust platform to boost highly active surface species in nanomaterials for a fundamental understanding of enhanced performance that may underpin future advances in electrocatalysis, photocatalysis, solar-energy conversion, and renewable-energy production.